Overview

This dissertation, The Role of Id-1 on the Proliferation, Motility and Mitotic Regulation of Prostate Epithelial Cells by Kaijun, Di, 狄凱軍, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled The role of Id-1 on the proliferation, motility and mitotic regulation of prostate epithelial cells Submitted by Kaijun Di for the degree of Doctor of Philosophy at The University of Hong Kong in October 2007 Id-1 is a member of the Id (inhibitor of differentiation or DNA binding) protein family that belongs to the helix-loop-helix (HLH) transcription factors. Id-1 is overexpressed in several human cancers, including prostate cancer, and its expression levels positively correlate with Gleason grading and poor clinical prognosis of cancer patients. Although numerous studies have explored the effects of Id-1 on the progression of prostate cancer, not much is known for the effect of Id-1 in prostate epithelial cells (PrECs). The aim of my project was to study the role of Id-1 on the proliferation, motility and mitotic regulation of non-malignant PrECs by either overexpression or inactivation of Id-1 expression levels. The first part of my study was to investigate if inactivation of Id-1 in the immortalized PrEC cell line, NPTX, might make cells more sensitive to the growth inhibitory effect of TGF-β1 (transforming growth factor-β1). The results showed that down-regulation of Id-1 suppressed cell proliferation and increased senescence, as well as enhanced cellular sensitivity to TGF-β1-induced growth arrest. These results implicate that Id-1 may be positively involved in cell proliferation and confer cellular resistance to TGF-β1-induced growth arrest, thus providing a growth advantage in non-malignant PrECs. The second part of my study was to investigate if overexpression of Id-1 in NPTX cells could confer more invasive and metastatic cell phenotypes in response to TGF-β1. I found that overexpression of Id-1 enhanced cell motility in response to TGF-β1 via promoting F-actin stress fiber formation, which was associated with increased cell-substrate adhesion and cell migration. This positive effect of Id-1 on TGF-β1-induced cell motility was mediated through activation of MEK-ERK signaling pathway and the subsequent activation of HSP27 (heat shock protein 27). In addition, Id-1 disrupted the adherens junction complex through down-regulation of E-cadherin, redistribution of β-catenin, and up-regulation of N-cadherin. These lines of evidence suggest that Id-1 may promote TGF-β1-induced cell motility, and intracellular Id-1 levels might be a determining factor for switching TGF-β1 from a tumor suppressor to a tumor promoter during prostate carcinogenesis. The third part of my study was to investigate the role of Id-1 in regulation of mitosis. Id-1 promoted chromosome instability through its effect on mitotic regulation, and it was found to co-localize with centrosome and mitotic spindles, and promote centrosome amplification. In addition, Id-1 was also shown to co-localize with Cdc20 (Cell division cycle protein 20) and Cdh1 (Cdc20 homolog 1), two co- activators of APC/C (anaphase promoting complex/cyclosome), and prevent Cdh1 degradation of Aurora A, a substrate of APC/C during mitotic exit. Therefore, Id- 1 may accelerate centrosome amplification and mitotic entry/exit, resulting in aneuploidy. In conclusion, Id-1 may promote prostate tumorigenesis in two aspects: On one hand, Id-1 may confer resistance to TGF-β1-induced growth arrest, and switch TGF-β1 from a tumor suppressor to a tumor promoter. On the

Full Product Details

9781361420393

Table of Contents

Reviews

Author Information

Tab Content 6

Customer Reviews

Recent Reviews

Countries Available